Antibiotic Management in Sepsis
Patients with sepsis should receive broad-spectrum antibiotics within one hour of recognition, with initial therapy consisting of an antipseudomonal beta-lactam such as piperacillin-tazobactam, ceftazidime/avibactam, or meropenem, with consideration of combination therapy for Pseudomonas infections or in immunocompromised patients. 1
Initial Antibiotic Selection and Timing
- Timing is critical: Administer IV antibiotics as early as possible, always within the first hour of recognizing sepsis or septic shock 1
- Obtain cultures first: Blood cultures should be drawn before starting antibiotics, but should not delay antibiotic administration 1
- Initial empiric coverage: Choose broad-spectrum antibiotics that cover the most likely pathogens based on:
- Suspected infection source
- Local resistance patterns
- Patient risk factors for resistant organisms
- Ability of the antibiotic to penetrate the presumed infection site 1
Recommended Empiric Regimens
First-line options:
- Antipseudomonal beta-lactam (one of the following):
Consider adding (for specific situations):
- Vancomycin (or alternative) when MRSA is suspected 1
- Aminoglycoside (e.g., gentamicin, amikacin) for suspected Pseudomonas or in neutropenic patients 1, 2
- Note: When administering piperacillin-tazobactam with aminoglycosides, they must be given separately due to in vitro inactivation 2
- Antifungal therapy when fungal infection is suspected 1
Source-Specific Considerations
- Intra-abdominal infection: Broad-spectrum coverage including anaerobes (piperacillin-tazobactam is excellent) 1
- Pyelonephritis: Third-generation cephalosporins or piperacillin/tazobactam 1
- Meningitis: Include meningeal-penetrating antibiotics 1
- Catheter-related: Remove infected catheters when possible for source control 1
De-escalation and Duration
- Daily assessment: Evaluate antibiotic regimen daily for de-escalation opportunities 1
- De-escalation timing: Narrow therapy once culture and susceptibility results are available (typically within 48-72 hours) 1
- Standard duration: 7-10 days for most cases of sepsis 1
- Consider shorter courses (5-7 days) for patients with rapid clinical resolution 1
- Consider longer courses for:
- Slow clinical response
- Undrainable foci of infection
- Staphylococcus aureus bacteremia (4-6 weeks)
- Immunocompromised patients 1
Special Populations
Pediatric Patients
- Early-onset sepsis (first 72 hours of life): Benzylpenicillin plus gentamicin or ampicillin plus gentamicin 1
- Late-onset sepsis (>72 hours to 1 month): Vancomycin for coagulase-negative staphylococci, and cefotaxime or piperacillin/tazobactam for GBS, E. coli, and enterococci 1
- Older children: Ceftriaxone (plus ampicillin or amoxicillin in infants up to 3 months) 1
Immunocompromised Patients
- Broader empiric coverage is warranted
- Consider antifungal therapy earlier
- Longer treatment courses may be necessary 1
Common Pitfalls to Avoid
- Delayed administration: Each hour delay in appropriate antibiotics increases mortality
- Inadequate initial coverage: Failure to cover likely pathogens leads to worse outcomes
- Failure to obtain cultures: Always obtain cultures before antibiotics when possible
- Inappropriate combination: When using piperacillin-tazobactam with aminoglycosides, they must be administered separately 2
- Failure to de-escalate: Continuing broad-spectrum therapy unnecessarily increases resistance risk
- Inadequate source control: Surgical drainage or device removal may be necessary 1
Monitoring Response
- Assess clinical response daily (vital signs, organ function, inflammatory markers)
- Consider procalcitonin levels to guide duration of therapy 1
- Evaluate for adverse effects of antimicrobial therapy
- Re-evaluate if clinical deterioration occurs despite appropriate therapy